ROS tyrosine kinase is a receptor-type protein tyrosine kinase similar to the EGF receptor, and it is considered that the ROS tyrosine kinase participates in signal transduction relative to proliferation and differentiation of cells (see, for example, Non-Patent Document 1).
Up to date, changes in the gene expression level of the ROS tyrosine kinase in some malignant tumors have been reported. For example, overexpression of the ROS tyrosine kinase is reported in glioma, meningioma, infiltrating ductal carcinoma, and so on (see, for example, Non-Patent Documents 2, 3 and 4), and chronic myelomonocytic leukemia (see, for example, Non-Patent Document 5).
In addition, there are found: FIG-ROS fusion gene in a glioblastoma cell line (see, for example, Non-Patent Document 6); SLC34A2-ROS fusion gene in a non-small cell lung cancer cell line (see, for example, Non-Patent Document 7); CD74-ROS fusion gene, FIG-ROS fusion gene, TPM3-ROS fusion gene, SDC4-ROS fusion gene, EZR-ROS fusion gene, LRIG3-ROS fusion gene, CCDC6-ROS fusion gene, and KDELR2-ROS fusion gene in non-small cell lung cancer clinical specimens (see, for example, Patent Documents 7, 8, 9, 10 and 11); FIG-ROS fusion gene in cholangiocarcinoma clinical specimens (see, for example, Non-Patent Document 12); FIG-ROS fusion gene in ovarian cancer clinical specimens (see, for example, Non-Patent Document 13); SLC34A2-ROS fusion gene in gastric cancer clinical specimens (see, for example, Non-Patent Document 14); CEP85L-ROS fusion gene in angiosarcoma clinical specimens (see, for example, Non-Patent Document 15); and YWHAE-ROS fusion gene and TFG-ROS1 fusion gene in inflammatory myofibroblastic tumor clinical specimens (see, for example, Non-Patent Document 16). It is reported that these fusion genes are oncogenes (see, for example, Non-Patent Documents 9 and 17). In addition, the ROS tyrosine kinase is a homologue of the transforming gene v-ros of the avian sarcoma virus (see, for example, Non-Patent Document 18), and it is considered that activation of the ROS tyrosine kinase is associated with oncogenesis.
Furthermore, even in liver cancer, kidney cancer, pancreatic cancer, testicular cancer (see, for example, Non-Patent Document 1), epithelioid hemangioendothelioma (see, for example, Non-Patent Document 15), colorectal cancer (see, for example, Non-Patent Document 19), liposarcoma, breast cancer (see, for example, Non-Patent Document 20), and Spitzoid neoplasms (see, for example, Non-Patent Document 21), a possibility of the presence of ROS fusion genes or occurrence of abnormality in the ROS tyrosine kinase is suggested.
Recently, it has been reported that crizotinib, which is a medicine having ROS inhibitory activity, is effective for patients of non-small cell lung cancer with ROS fusion gene positive in the clinical application (see, for example, Non-Patent Document 22).
From the foregoing, it is considered that the ROS tyrosine kinase inhibitor is effective as a treating agent for the malignant tumors as described previously.
In addition, overexpression of an ROS tyrosine kinase is seen in interstitial pneumonia, and a possibility that the ROS tyrosine kinase plays an important role for the onset of interstitial pneumonia is suggested (see, for example, Non-Patent Document 23); and a possibility that the ROS tyrosine kinase inhibitor is effective for the interstitial pneumonia is considered. Furthermore, in view of the fact that ROS tyrosine kinase knockout male mice are male infertile, a possibility that the ROS tyrosine kinase inhibitor is effective as a male contraceptive is considered (see, for example, Non-Patent Documents 24 and 25).